DESCRIPTION (Applicant's Abstract): This application proposes a clinical pilot study of anterior nucleus thalamic stimulation (ANTS) as a treatment for intractable epilepsy, in order to lay the groundwork for a larger randomized, controlled clinical trial. Studies by the principal investigator and others have suggested that thalamic stimulation is useful for treatment of seizures in animal models and potentially in patients. Epilepsy affects about 1% of the U.S. population, and approximately 25% are not helped by existing therapies. Therefore, the need for new therapies is great. Study subjects will have partial epilepsy with or without secondarily generalized seizures, at least 10 per month, and not responsive to standard medical or surgical therapies. Stimulating electrodes will be implanted bilaterally in the anterior nucleus of thalamus and connected subcutaneously to subclavicular stimulators. A combination of physiological and anatomical techniques will be used to verify proper electrode placements. Stimulation will be delivered continuously as 90 microsecond pulses at 100/s, for one minute on and five minutes off, at five Volts amplitude. A blinded lead-in design will be used to establish safety and a preliminary evaluation of efficacy of this therapy. Specific aims of the pilot trial will be to establish that ANTS targeting can be accomplished in the operating room with accuracy of 5 mm or better. The pilot will show that it is possible to develop a suitable double-blind test protocol. The study will establish that a high level of stimulation at 5 V, 90 us, 100 Hz is as well-tolerated as is a low level of stimulation at 1 V, 90 us, 100 Hz, thereby allowing future trials to use high levels of stimulation. Sub-projects to be done at selected study sites will determine whether PET scans can provide metabolic maps of brain sites activated by thalamic stimulation, whether EEG spikes and seizures can be recorded from ANT, whether unit recording increases accuracy of electrode placement, and whether ANTS affects neuropsychologic testing. The pilot study will serve to develop a group of investigators experienced with ANTS for future trials, to identify institutions at which the protocol successfully can be completed, and to provide an accurate sample size estimate for a definitive trial. A consortium of centers experienced in epilepsy research will collaborate on this project, which will move brain stimulation for epilepsy into the realm of a testable new therapy for intractable seizures.